Polarized gas accumulators and heating jackets and associated gas collection methods and thaw methods and polarized gas products

ABSTRACT

Methods of collecting, thawing, and extending the useful polarized life of frozen polarized gases include heating a portion of the flow path and/or directly liquefying the frozen gas during thawing. A polarized noble gas product with an extended polarized life product is also included. Associated apparatus such as an accumulator and heating jacket for collecting, storing, and transporting polarized noble gases include a secondary flow channel which provides heat to a portion of the collection path during accumulation and during thawing.

RELATED APPLICATIONS

This application is a divisional of U.S. patent application Ser. No.09/210,020, filed Dec. 11, 1998, which claims priority from ProvisionalApplication Ser. No. 60/069,435, filed Dec. 12, 1997. This applicationis also related to U.S. Pat. No. 6,079,213.

This invention was made with Government support under AFSOR Grant numberF41624-97-C-9001. The United States Government has certain rights inthis invention.

FIELD OF THE INVENTION

The present invention relates to the collection and accumulation ofpolarized noble gases, and relates more particularly to the productionof hyperpolarized gases for use in medical diagnostic procedures such asmagnetic resonance imaging (“MRI”) and spectroscopy applications.

BACKGROUND OF THE INVENTION

Conventionally, MRI has been used to produce images by exciting thenuclei of hydrogen molecules (present in water protons) in the humanbody. However, it has recently been discovered that polarized noblegases can produce improved images of certain areas and regions of thebody which have heretofore produced less than satisfactory images inthis modality. Polarized Helium 3 (“³He”) and Xenon-129 (“¹²⁹Xe”) havebeen found to be particularly suited for this purpose. Unfortunately, aswill be discussed further below, the polarized state of the gases issensitive to handling and environmental conditions and can, undesirably,decay from the polarized state relatively quickly.

Hyperpolarizers are used to produce and accumulate polarized noblegases. Hyperpolarizers artificially enhance the polarization of certainnoble gas nuclei (such as ¹²⁹Xe or ³He) over the natural or equilibriumlevels, i.e., the Boltzmann polarization. Such an increase is desirablebecause it enhances and increases the Magnetic Resonance Imaging (“MRI”)signal intensity, allowing physicians to obtain better images of thesubstance in the body. See U.S. Pat. No. 5,545,396 to Albert et al., thedisclosure of which is hereby incorporated herein by reference as ifrecited in full herein.

In order to produce the hyperpolarized gas, the noble gas is typicallyblended with optically pumped alkali metal vapors such as rubidium(“Rb”). These optically pumped metal vapors collide with the nuclei ofthe noble gas and hyperpolarize the noble gas through a phenomenon knownas “spin-exchange”. The “optical pumping” of the alkali metal vapor isproduced by irradiating the alkali-metal vapor with circularly polarizedlight at the wavelength of the first principal resonance for the alkalimetal (e.g., 795 nm for Rb). Generally stated, the ground state atomsbecome excited, then subsequently decay back to the ground state. Undera modest magnetic field (10 Gauss), the cycling of atoms between theground and excited states can yield nearly 100% polarization of theatoms in a few microseconds. This polarization is generally carried bythe lone valence electron characteristics of the alkali metal. In thepresence of non-zero nuclear spin noble gases, the alkali-metal vaporatoms can collide with the noble gas atoms in a manner in which thepolarization of the valence electrons is transferred to the noble-gasnuclei through a mutual spin flip “spin-exchange”.

Conventionally, lasers have been used to optically pump the alkalimetals. Various lasers emit light signals over various wavelength bands.In order to improve the optical pumping process for certain types oflasers (particularly those with broader bandwidth emissions), theabsorption or resonance line width of the alkali metal can be madebroader to more closely correspond with the particular laser emissionbandwidth of the selected laser. This broadening can be achieved bypressure broadening, i.e., by using a buffer gas in the optical pumpingchamber. Collisions of the alkali metal vapor with a buffer gas willlead to a broadening of the alkali's absorption bandwidth.

For example, it is known that the amount of polarized ¹²⁹Xe which can beproduced per unit time is directly proportional to the light powerabsorbed by the Rb vapor. Thus, polarizing ¹²⁹Xe in large quantitiesgenerally takes a large amount of laser power. When using a diode laserarray, the natural Rb absorption line bandwidth is typically many timesnarrower than the laser emission bandwidth. The Rb absorption range canbe increased by using a buffer gas. Of course, the selection of a buffergas can also undesirably impact the Rb-noble gas spin-exchange bypotentially introducing an angular momentum loss of the alkali metal tothe buffer gas rather than to the noble gas as desired.

In any event, after the spin-exchange has been completed, thehyperpolarized gas is separated from the alkali metal prior tointroduction into a patient. Unfortunately, after and during collection,the hyperpolarized gas can deteriorate or decay relatively quickly (loseits hyperpolarized state) and therefore must be handled, collected,transported, and stored carefully. Thus, handling of the hyperpolarizedgases is critical, because of the sensitivity of the hyperpolarizedstate to environmental and handling factors and the potential forundesirable decay of the gas from its hyperpolarized state.

Some accumulation systems employ cryogenic accumulators to separate thebuffer gas from the polarized gas and to freeze the collected polarizedgas. Unfortunately, reductions in polarization of the gas can beproblematic as, after final thawing of the frozen gas, the polarizationlevel of the gas can potentially be undesirably reduced by as much as anorder of magnitude. Further and disadvantageously, the extremely lowoperating temperatures of the accumulator near the cryogen source cansometimes clog the collection area of the accumulator, therebydecreasing the rate of, or even preventing, further collection.

OBJECTS AND SUMMARY OF THE INVENTION

In view of the foregoing, it is therefore an object of the presentinvention to extend the polarization life of collected polarized noblegases and to reduce the amount of de-polarization in the collectedpolarized gas prior to the end use point.

It is another object of the present invention to provide an improvedcryogenic accumulator which can be used in a substantially continuousproduction environment.

It is a further object of the present invention to provide an improvedcollection device and method which reduces the amount of polarizationlost during processing.

It is yet another object of the invention to provide a method which willminimize the de-polarization effects attributed to thawing a frozenpolarized gas product prior to delivery to an end user.

These and other objects are satisfied by the present invention by acryogenic accumulator with an internal heating jacket. In particular, afirst aspect of the invention is directed to a cryogenic accumulator forcollecting polarized noble gases which includes a primary flow channelhaving opposing first and second ends configured to direct polarized gastherethrough, and an outer sleeve positioned around the primary flowchannel. The outer sleeve has a closed end defining a collection chamberpositioned below the flow channel second end. The accumulator alsoincludes a secondary flow channel positioned intermediate of the primaryflow channel and the outer sleeve. The secondary flow channel has aclosed end positioned in close proximity to the primary flow channelsecond end.

In a preferred embodiment, the outer sleeve and the outer wall of thesecondary flow channel define a buffer gas exit channel therebetween andthe (circumferentially extending) inner wall of the secondary flowchannel defines the primary flow channel. It is also preferred that theprimary flow channel second end be configured as a nozzle and that thesecondary flow channel be configured as a warming or heating jacket todirect circulating room temperature dry gases such as nitrogentherethrough. The circulating nitrogen is separate from the flow channeland acts to compensate or protect the nozzle area against the coldbuffer gas exiting along the outside of the primary flow channel and thecryogenic temperatures associated with the cryogen bath. Advantageously,such a secondary flow channel can reduce the likelihood that the primaryflow nozzle will freeze and clog from sublimation of the noble gas.

Further and preferably, the accumulator includes first and secondisolation valves in communication with the primary flow channel and thebuffer gas exit channel. The first isolation valve is positioned at thefirst end of the primary flow channel and can be used to control theflow of a target gas therethrough. The second isolation valve ispositioned spaced-apart from the outer sleeve closed end along thebuffer gas exit channel to releasably seal and control the release ofbuffer gas therethrough. In this embodiment, the accumulator isconfigured to contain MRI-sized quantities (such as 0.5-2 liters ofpolarized gas) and is detachably releasable from a hyperpolarizer unitfor easy transport to a remote site.

Another aspect of the present invention relates to a heating jacket fora refrigerated accumulator. The jacket includes an outer wall havingopposing first and second ends and an inner wall having opposing firstand second ends. The inner wall is spaced apart from the outer wall. Theinner wall is configured to be in close proximity to a polarized gascollection path. The jacket also includes a top and bottom which bridgeand seal each of the outer and inner walls. The top, bottom and outerand inner walls define at least one enclosed fluid (such as a gas orliquid) circulation channel therebetween. The jacket also includes afluid and a fluid vent, each of which is in communication with thecirculation channel. The fluid inlet and vent are configured to allowflow of a fluid, gas, or gas mixture in the circulation channel.

In a preferred embodiment, the heating jacket fluid inlet is operablyassociated with a valve such that it is configured to provide apredetermined flow rate of the gas in the circulation channel. It isalso preferred that the inner wall circumferentially extends around acenter opening to define a flow channel therethrough for a polarizedgas.

It is additionally preferred that the inner wall include a first portionwhich defines a flow channel first diameter and a stepped down portionwhich defines a flow channel second diameter. In this embodiment, thesecond diameter is smaller than the first diameter and defines a flowchannel nozzle.

Yet another aspect of the instant invention is directed to anaccumulator for collecting a polarized gas. The accumulator comprises aprimary flow channel having opposing inlet and exit ends, with the exitend being configured as a flow nozzle. The inlet end is detachablyconnected to a polarized gas collection path. The accumulator alsoincludes an outer sleeve with a collection chamber aligned with andpositioned adjacent to the flow nozzle. In a preferred embodiment, theaccumulator includes a heat source such as the enclosed heating jacketas described above. In operation, the heat source is arranged in thedevice to heat the flow nozzle to prevent clogging or freezing of thepolarized gas thereat. An accumulator with a nozzle in the primary flowpath can help remove and trap all of the hyperpolarized gas from theinlet stream, reducing any waste of exiting polarized gases. The use ofa nozzle improves localization of polarized gases such as ¹²⁹Xe.Further, such a nozzle can minimize the heat load on accumulated ¹²⁹Xe(thus lengthening its relaxation or decay time). The use of a warmingjacket can allow the use of a nozzle in the cryogen flow area and canimprove the operation or function of the nozzle by reducing any cloggingin the nozzle area of the flow path.

An additional aspect of the present invention is directed to a methodfor collecting polarized noble gases. The method includes directing agas mixture comprising a polarized noble gas into a collection path. Thegas mixture is received into an accumulator positioned in the collectionpath. The accumulator has an inlet channel, a collection reservoir, andan exit channel. The collection reservoir is exposed to temperaturesbelow the freezing point of the polarized noble gas. The polarized noblegas is trapped in a substantially frozen state in the collectionreservoir. The remainder of the gas mixture is routed into the exitchannel. A portion of the collection path is heated or warmed tofacilitate the flow of the gas mixture therethrough. Preferably, theheating step includes the steps of introducing a gas separate from thegas mixture into a predetermined area of the inlet path, thepredetermined area being contained apart from the inlet path. The gas iscirculated separate from the gas mixture about a portion of the inletpath to provide conductive heat to at least a portion of the inlet pathand thereby reduce the likelihood blockage along the inlet pathattributed to the exposing step. Preferably, the heating is provided bycirculating room temperature N₂ gas around the outside of at least aportion of the inlet path channel. The N₂ gas is then captured andvented to atmosphere away from the frozen accumulated noble gas.

Yet another aspect of the present invention is a method of thawingfrozen polarized gas. In this method, a sealed container is provided.The container has an interior flow path and a collection chamber, thecollection chamber is configured to hold frozen polarized gas therein.The frozen polarized gas is exposed to a magnetic field. A portion ofthe interior flow path adjacent the collection chamber is heated and theexterior of the sealed container is heated. Preferably, the thawing stepis performed under pressure such that a substantial portion of thefrozen noble gas is liquified during thawing of the frozen polarizedgas. In a preferred embodiment, the container includes two valves, andafter the frozen product is liquified, at least one of the valves isopened to decrease the pressure in the container causing the liquifiedgas to rapidly become gaseous. At this point, the flow of the gas ispreferably directed to a patient. This step is typically accomplished bycollecting the gas in a bag or other type of receptacle and deliveringit to the patient. This method quickly thaws the frozen gas andminimizes the time the polarized gas spends in the transition phasewhich can improve the polarization levels retained upon thaw. Further,the instant thawing method can decrease the thawing time overconventional methods to less than 10 seconds for single patient MRIdoses. In a preferred embodiment, the ¹²⁹Xe gas mixture which isintroduced into the polarizer includes a minimal amount of ¹³¹Xe tominimize decay associated with the ¹³¹Xe induced relaxation of the ¹²⁹Xeisotope.

Yet another aspect of the present invention relates to a method ofextending the useful polarized life of a polarized gas product. Themethod includes the steps of providing a magnetic field and freezing apolarized gas in the presence of the magnetic field. The polarized gasis sealed in a containment device or vessel. The frozen polarized gas isthen thawed at a desired time. A substantial portion of the frozen gasis liquified under pressure in the sealed container. Preferably, thethawing step includes the heating steps as described above (heating bothan interior and exterior of the sealed container). In any event, in oneembodiment, the containment device is depressurized causing the liquidto become gas. More preferably, the depressurizing step is carried outby opening the containment device to a collection vessel and allowingthe liquid to expand into a gas phase during delivery of the polarizedgas to an end user.

Advantageously, such a method can increase the polarization level in thethawed polarized gas over conventional processing methods. Indeed, theinstant invention can double the polarization levels retained in gassamples processed by conventional methods. Further and additionallyadvantageously, the instant invention provides an improved accumulatorwhich can improve the accumulation and the preservation of thehyperpolarized state of the noble gas. Conventional thawing andaccumulation techniques significantly reduced polarizations belowpredicted values (typically to about only 12.2% from its startingpolarization levels at 900 sccm—losing 87.8% of its startingpolarization). The instant invention can improve the preservation of thepolarization substantially. For example, the improved accumulation andthawing methods can retain at least 30% or more (and preferably about40%-50%) post-thaw polarization from the initial pre-frozen polarizationlevels (“the polarization retention fraction”). Further, the instantinvention can provide polarization levels at 10% or more at the time ofdelivery to a patient or end user. In addition, the instant inventioncan collect additional amounts of polarized gas in a period by improvingthe delivery path and reducing the potential of the cold finger to blockwith frozen gas and the like during collection.

The foregoing and other objects and aspects of the present invention areexplained in detail herein.

BRIEF DESCRIPTION OF THE DRAWING

FIG. 1 is a schematic illustration of a hyperpolarizer apparatusaccording to one embodiment of the present invention.

FIG. 2 is a side perspective view of an accumulator or “cold finger” ofthe apparatus of FIG. 1 partially immersed in a liquid cryogen accordingto one embodiment of the present invention.

FIG. 3 is a cross-sectional side view of an accumulator of FIG. 2according to one embodiment of the present invention.

FIG. 4 is a front view of the accumulator illustrated in FIG. 3.

FIG. 5 is a cross-sectional side view of an additional embodiment of anaccumulator of the present invention.

FIG. 6 is a partial cutaway perspective view of the accumulatorillustrated in FIG. 3.

FIG. 7 is a partial cutaway perspective view of the accumulatorillustrated in FIG. 5.

FIG. 8 illustrates the accumulator of FIG. 7 with heat applied during athawing process according to one embodiment of the present invention.

FIG. 9 is a block diagram illustrating the steps of a method foraccumulating polarized gas according to the present invention.

FIG. 10 is a block diagram illustrating the steps of a method forthawing frozen polarized gas according to one embodiment of the presentinvention.

FIG. 11 is a block diagram illustrating the steps of a method forextending the useful life of a polarized gas according to one embodimentof the present invention.

FIG. 12A graphically illustrates polarization levels after thaw versusaccumulation flow rates of a polarized gas thawed using a conventionalthaw method.

FIG. 12B graphically illustrates exemplary polarization levels afterthaw versus accumulation flow rates of a polarized gas thawed accordingto the present invention.

FIG. 13 graphically illustrates exemplary polarization levels ofpolarized gas before freezing and after thawing according to the presentinvention.

FIG. 13A graphically illustrates predicted and experimental exemplarypolarization levels of polarized xenon corresponding to the polarizationflow rate for post-thaw experimental data taken when the xenon isprocessed according to the present invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention will now be described more fully hereinafter withreference to the accompanying figures, in which preferred embodiments ofthe invention are shown. This invention may, however, be embodied inmany different forms and should not be construed as limited to theembodiments set forth herein. Like numbers refer to like elementsthroughout. Layers and regions may be exaggerated for clarity. In thedescription of the present invention that follows, certain terms areemployed to refer to the positional relationship of certain structuresrelative to other structures. As used herein the term “forward” andderivatives thereof refer to the general direction the gas mixturetravels as it moves through the hyperpolarizer unit; this term is meantto be synonymous with the term “downstream” which is often used inmanufacturing environments to indicate that certain material being actedupon is farther along in the manufacturing process than other material.Conversely, the terms “rearward” and “upstream” and derivatives thereofrefer to the directions opposite, respectively, the forward anddownstream directions. Also, as described herein, polarized gases arecollected, frozen, thawed, and used in MRI spectroscopy or MRIapplications. For ease of description, the term “frozen polarized gas”means that the polarized gas has been frozen into a solid state. Theterm “liquid polarized gas” means that the polarized gas has been or isbeing liquefied into a liquid state. Thus, although each term includesthe word “gas”, this word is used to name and descriptively track thegas which is produced via a hyperpolarizer to obtain a polarized “gas”product. Thus, as used herein, the term gas has been used in certainplaces to descriptively indicate a hyperpolarized noble gas product andmay be used with modifiers such as solid, frozen, and liquid to describethe state or phase of that product.

Various techniques have been employed to accumulate and capturepolarized gases. For example, U.S. Pat. No. 5,642,625 to Cates et al.,describes a high volume hyperpolarizer for spin polarized noble gas andU.S. patent application No. 08/622,865 to Cates et al. describes acryogenic accumulator for spin-polarized ¹²⁹Xe. These references arehereby incorporated by reference as if recited in full herein. As usedherein, the terms “hyperpolarize” “polarize”, and the like, mean toartificially enhance the polarization of certain noble gas nuclei overthe natural or equilibrium levels. Such an increase is desirable becauseit allows stronger imaging signals corresponding to better MRI images ofthe substance and a targeted area of the body. As is known by those ofskill in the art, hyperpolarization can be induced by spin-exchange withan optically pumped alkali-metal vapor or alternatively by metastabilityexchange. See Albert et al., U.S. Pat. No. 5,545,396.

Referring to the drawings, FIG. 1 illustrates a preferred hyperpolarizerunit 10. This unit is a high volume unit which is configured tocontinually produce and accumulate spin-polarized noble gases, i.e., theflow of gas through the unit is substantially continuous. As shown, theunit 10 includes a noble gas supply 12 and a supply regulator 14. Apurifier 16 is positioned in the line to remove impurities such as watervapor from the system as will be discussed further below. Thehyperpolarizer unit 10 also includes a flow meter 18 and an inlet valve20 positioned upstream of the polarizer cell 22. An optic light sourcesuch as a laser 26 (preferably a diode laser array) is directed into thepolarizer cell 22 through various focusing and light distributing means24, such as lenses, mirrors, and the like. The light source iscircularly polarized to optically pump the alkali metals in the cell 22.An additional valve 28 is positioned downstream of the polarizer cell22.

Next in line, as shown in FIG. 1, is a cold finger or accumulator 30.The accumulator 30 is connected to the hyperpolarizer unit 10 by a pairof releasable mechanisms such as threaded members or quick disconnects31, 32. This allows the accumulator to be easily detached, removed, oradded, to and from the system 10. The accumulator 30 is operablyassociated with a cold source or refrigeration means 42. Preferably, andas shown, the cold source 42 is a liquid cryogen bath 43. Theaccumulator will be discussed in more detail hereinbelow.

A vacuum pump 60 is in communication with the system. Additional valvesto control flow and direct exit gas are shown at various points (shownas 52, 55). A shut-off valve 47 is positioned adjacent an “on-board”exit gas tap 50. Certain of the valves downstream of the accumulator 30are used for “on-board” thawing and delivery of the collected polarizedgas as will be described further below. The system also includes adigital pressure transducer 54 and a flow control means 57 along with ashut-off valve 58. The shut-off valve 58 preferably controls the flow ofgas through the entire system or unit 10; it is used to turn the gasflow on and off, as will be described below. As will be understood bythose of skill in the art, other flow control mechanisms, devices(analog and electronic) may be used within the scope of the presentinvention.

In operation, a gas mixture is introduced into the system at the gassource 12.

As shown in FIG. 1, the source 12 is a pressurized gas tank which holdsa pre-mixed gas mixture. The gas mixture includes a lean noble andbuffer gas mixture gas (the gas to be hyperpolarized is present as arelatively small amount in the premixed gas mixture). Preferably, forproducing hyperpolarized ¹²⁹Xe, the pre-mixed gas mixture is about95-98% He, about 5% or less ¹²⁹Xe, and about 1% N₂.

It is also preferred that the pre-mixed gas mixture comprises a minimalamount of the xenon-131 (or ¹³¹Xenon) isotope (reduced from its naturallevels). In nature, the typical xenon isotopic abundances are asfollows:

TABLE I Isotope Abundance Nuclear Spin ¹²⁴Xe 0.1% 0 ¹²⁶Xe 0.09% 0 ¹²⁸Xe1.91% 0 ¹²⁹Xe 26.4% ½ ¹³⁰Xe 4.1% 0 ¹³¹Xe 21.2% {fraction (3/2)} ¹³²Xe26.9% 0 ¹³⁴Xe 10.4% 0 ¹³⁶Xe 8.9% 0

“Enriched” ¹²⁹Xe mixtures are used to provide sufficient amounts of the¹²⁹Xe gas for the hyperpolarized gas mixture. As used herein, the form“enriched” means increasing the abundance of ¹²⁹Xe over its naturalabundance level. However, the enriched ¹²⁹Xe typically also includesother Xenon isotopes. Unfortunately, at least one particularisotope-¹³¹Xe can interact with frozen ¹²⁹Xe (particularly at lowtemperatures such as 4.2° K) in a manner which can cause the 129Xe todepolarize. At low temperatures, the ¹³¹Xe acts like a “spin-sink” toabsorb or decay the ¹²⁹Xe polarization and becoming a potentiallydominant relaxation mechanism at the crystal grain boundaries of thefrozen “solid” ¹²⁹Xe polarized gas.

As shown in Table I above, ¹³¹Xe is an isotope with a nuclear spingreater than one-half. As such, it has a “quadruple moment” which meansthat ¹³¹Xe is able to relax by interacting with electric fieldgradients. See Gatzke et al., Extraordinarily slow nuclear spin relationin frozen laser-polarized 129Xe, Phys. Rev. Lett. 70, pp. 690-693(1993).

It has been suggested that at 4.20° K, the dominant solid phaserelaxation mechanism is “cross-relaxation” between the ¹²⁹Xe and ¹³¹Xeisotopes at the crystal grain boundaries. In addition, where the“frozen” or “solid” ¹²⁹Xe gas takes on a form similar to a flake (suchas a snowflake) the form has a relatively large surface area.Unfortunately, this relatively large surface area can also allow greaterdepolarizing interactions with the ¹³¹Xe. It is believed that thegreatest or “most-efficient” interchange is at the crystal grainboundaries because that is typically where the electric fields arestrongest. This electric field strength can then allow the ¹³¹Xe nuclearspin flip energy to become nearly the same as the ¹²⁹Xe nuclear spinflip energy.

Examples of enriched ¹²⁹Xe mixtures with a reduced ¹³¹Xe isotope contentare given below.

EXAMPLE 1

82.3% Enriched ¹²⁹Xe Gas Mixture.

Isotope Abundance Nuclear Spin ¹²⁴Xe 0.47% 0 ¹²⁶Xe 0.43% 0 ¹²⁸Xe 8.41% 0¹²⁹Xe 82.3% ½ ¹³⁰Xe 4.52% 0 ¹³¹Xe 3.45% {fraction (3/2)} ¹³²Xe 0.36% 0¹³⁴Xe 0.01% 0 ¹³⁶Xe 0.01% 0

EXAMPLE 2

47.2% Enriched ¹²⁹Xe Gas Mixture.

Isotope Abundance Nuclear Spin ¹²⁴Xe 0.14% 0 ¹²⁶Xe 0.28% 0 ¹²⁸Xe 52.0% 0¹²⁹Xe 47.2% ½ ¹³⁰Xe 0.22% 0 ¹³¹Xe 0.09% {fraction (3/2)} ¹³²Xe 0.03% 0¹³⁴Xe 0.02% 0 ¹³⁶Xe 0.02% 0

In a preferred embodiment, when the collected polarized ¹²⁹Xe will beexposed to cold temperatures and frozen, the enriched ¹²⁹Xe gas mixturepreferably includes less than about 3.5% ¹³¹Xe, and more preferably lessthan about 0.1% ¹³¹Xe.

In any event, the gas “enriched” mixture is passed through the purifier16 and introduced into the polarizer cell 22. The valves 20, 28 areon/off valves operably associated with the polarizer cell 22. The gasregulator 14 preferably steps down the pressure from the gas tank source12 (typically operating at 13,780.2 kPa (2000 psi or 136 atm)) to about608-1013.25 kPa (6-10 atm) for the system. Thus, during accumulation,the entire manifold (conduit, polarized cell, accumulator, etc.) ispressurized to the cell pressure (about 608-1013.25 kPa (6-10 atm)). Theflow in the unit 10 is activated by opening valve 58 and is controlledby adjusting the flow control means 57.

The typical residence time of the gas in the cell 22 is about 10-30seconds; i.e., it takes on the order of 10-30 seconds for the gasmixture to be hyperpolarized while moving through the cell 22. The gasmixture is preferably introduced into the cell 22 at a pressure of about608-1013.25 kPa (6-10 atm). Of course, with hardware capable ofoperating at increased pressures, operating pressures of above 1013.25kPa (10 atm), such as about 2026.5-3039.75 kPa (20-30 atm) are preferredto pressure broaden the Rb and absorb up to 100% of the optical light.In contrast, for laser linewidths less than conventional linewidths,lower pressures can be employed. The polarizer cell 22 is a highpressure optical pumping cell housed in a heated chamber with aperturesconfigured to allow entry of the laser emitted light. Preferably, thehyperpolarizer unit 10 hyperpolarizes a selected noble gas such as ¹²⁹Xe(or ³He) via a conventional spin-exchange process. A vaporized alkalimetal such as rubidium (“Rb”) is introduced into the polarizer cell 22.The Rb vapor is optically pumped via an optic light source 26,preferably a diode laser.

The unit 10 employs helium buffer gas to pressure broaden the Rb vaporabsorption bandwidth. The selection of a buffer gas is important becausethe buffer gas—while broadening the absorption bandwidth—can alsoundesirably impact the alkali metal-noble gas spin-exchange bypotentially introducing an angular momentum loss of the alkali metal tothe buffer gas rather than to the noble gas as desired. In a preferredembodiment, ¹²⁹Xe is hyperpolarized through spin exchange with theoptically pumped Rb vapor. It is also preferred that the unit 10 uses ahelium buffer gas with a pressure many times greater than the ¹²⁹Xepressure for pressure broadening in a manner which minimizes Rb spindestruction.

As will be appreciated by those of skill in the art, Rb is reactive withH₂O. Therefore any water or water vapor introduced into the polarizercell 22 can cause the Rb to lose laser absorption and decrease theamount or efficiency of the spin-exchange in the polarizer cell 22.Thus, as an additional precaution, an extra filter or purifier (notshown) can be positioned before the inlet of the polarizer cell 22 withextra surface area to remove even additional amounts of this undesirableimpurity in order to further increase the efficiency of the polarizer.

Hyperpolarized gas, together with the buffer gas mixture, exits thepolarizer cell 22 and enters the accumulator 30. Referring now to FIGS.3-7, the polarized gas and buffer gas are directed down a primary flowpath 80 and into a collection reservoir 75 located at the bottom of theaccumulator 30. In operation, at the lower portion of the accumulator 30a, the hyperpolarized gas is exposed to temperatures below its freezingpoint and collected as a frozen product 100 in the reservoir 75. Theremainder of the gas mixture remains gaseous and exits the primary flowpath 80 and the reservoir 75 by counterflowing in an exit path 90different from the primary flow path 75 such that it is directed out ofthe accumulator 30. The accumulator 30 will be discussed in more detailbelow. The hyperpolarized gas is collected (as well as stored,transported, and preferably thawed) in the presence of a magnetic field,generally on the order of at least 500 Gauss, and typically about 2kiloGauss, although higher fields can be used. Lower fields canpotentially undesirably increase the relaxation rate or decrease therelaxation time of the polarized gas. As shown in FIG. 2, the magneticfield is provided by permanent magnets 40 positioned about a magneticyoke 41.

The hyperpolarizer unit 10 can also use the temperature change in theoutlet line between the heated pumping cell 22 and the refrigerated coldtrap or accumulator 30 to precipitate the alkali metal from thepolarized gas stream in the conduit above the accumulator 30. As will beappreciated by one of skill in the art, the alkali metal can precipitateout of the gas stream at temperatures of about 40° C. The unit can alsoinclude an alkali metal reflux condenser (not shown). Preferably, therefluxing condenser employs a vertical refluxing outlet pipe, which iskept at room temperature. The gas flow velocity through the refluxingpipe and the size of the refluxing outlet pipe is such that the alkalimetal vapor condenses and drips back into the pumping cell bygravitational force. In any event, it is desirable to remove the alkalimetal such that the product is non-toxic and comply with regulatorystandards (for example at least to a level at or below 10 ppb) prior todelivering polarized gas to a patient.

Optionally, an intermediate cold trap can also be positioned between theexit of the polarizer cell 22 and the cold finger 30. The temperature ofthe intermediate cold trap (not shown) will preferably be designed totrap out any alkali metal (e.g. Rb) while leaving the noble gas andcarrier gas (es) free to reach the cold finger 30. This can be importantfor in vivo applications where it is important to remove the Rb from thehyperpolarized gas (i.e., remove the Rb to a level such that no morethan trace amounts such as on the order of one ppb or less remains inthe hyperpolarized gas when delivered to a patient).

Once a desired amount of hyperpolarized gas has been collected in theaccumulator 30, the accumulator can be detached or isolated from thesystem. In a preferred embodiment, valve 28 is closed, leaving the cell22 pressurized. This allows the accumulator 30 and the downstreamplumbing to begin to depressurize because the flow valve 58 is open.Preferably, the unit 10 downstream of the valve 28 is allowed todepressurize to about 1.5 atm before the flow valve 58 is closed. Afterclosing the flow valve 58, valve 55 can be opened to evacuate theremaining gas in the manifold. Once the outlet plumbing is evacuated,valves 35 and 37 are closed. If the collected gas is to be distributed“on board”, i.e., without removing the accumulator 30 from the unit 10,a receptacle such as a bag or other vessel can be attached to the outlet50. The valve 47 can be opened to evacuate the attached bag (not shown).Once the bag is evacuated and the gas is ready to thaw, valve 52 can beoptionally closed. This minimizes the contact of the polarized gas withthe pressure transducer region 59 of the unit 10. This region typicallyincludes materials that have a depolarizing effect on the polarized gas.Thus, long contact times with this region may promote relaxation of thepolarized gas.

If the valve 52 is not closed, then valve 55 is preferably closed toprevent the evacuation of polarized thawed gases. It is also preferredthat the flow channels on the downstream side of the cell 22 are formedfrom materials which minimize the decaying effect on the polarized stateof the gas. Coatings can also be used such as those described in U.S.Pat. No. 5,612,103, the disclosure of which is hereby incorporated byreference as if recited in full herein. In the “on-board” thawoperation, valve 37 is opened to let the gas out. It then proceedsthrough valve 47 and exits outlet 50.

In the “detached” or “transported accumulator” thaw mode, accumulatorfirst and second isolation valves 35, 37 are closed after thedepressurization and evacuation of the accumulator 30. Evacuating theaccumulator 30 allows any residual gas in the accumulator to be removed.Leaving residual gas in the accumulator 30 with the frozen polarized gasmay contribute to the heat load on the frozen gas, possibly raising thetemperature of the frozen gas and potentially shortening the relaxationtime. Thus, in a preferred embodiment, after depressurization andevacuation and closing the isolation valves 35, 37, the accumulator 30is disconnected from the unit 10 via release points 31, 32.

It is also preferred that the accumulator include O-rings in grooves(FIG. 2, 220) to assist in sealing the quick connects (or otherattaching means) to the conduit lines in the system. This type ofO-ring/groove sealing mechanism can help assure the seals integrity evenat the elevated operating pressures (i.e., 608-1013.25 kPa (6-10 atm)and greater) of the unit. Similarly, if CHEM-THREADS™ (manufactured byChemGlass, Inc. Vineland, N.J.) or similar attachment means are used, itis preferred that they be configured to hold pressures consistent withthe operating pressures of the system. Examples of suitable isolationvalves 35, 37 include KIMBLE KONTES Valves 826450-004, 826460-0004located in Vineland, N.J.

The isolation valves 35, 37 are in communication with the primary flowchannel 80 and the buffer gas exit channel 90 respectively and each canadjust the amount of flow therethrough as well as close the respectivepaths to isolate the accumulator from the system 10 and the environment.After the filled accumulator 30 is removed, another accumulator can beeasily and relatively quickly attached to the release points 31, 32.Preferably, when attaching the new accumulator 30, the outlet manifoldis evacuated using valve 55 (with valves 52, 35, 37 open). When asuitable vacuum is achieved (such as about 13.3 Pa (100 milliTorr))which typically occurs within about one minute or so, valve 55 isclosed. Valve 28 is then re-opened which repressurizes the outletmanifold to the operating cell pressure. Valve 58 is then opened toresume flow in the unit 10. Preferably, once flow resumes, liquidnitrogen is applied to the accumulator 30 to continue collection of thehyperpolarized gas. Typically such a changeover takes on the order ofless than about five minutes. Thus, a preferred hyperpolarizer unit 10is configured to provide a continuous flow of hyperpolarized ¹²⁹Xe gasfor continuous production and accumulation of same.

Turning now to FIG. 2, an accumulator and magnet yoke assembly 230 isshown. The accumulator 30 is supported by a support platform 210positioned over the cryogen bath 43. A pair of plates 215 longitudinallyextend from the support platform 210 and connect to the magnet yoke 41.The magnet yoke 41 is positioned adjacent to and in close proximity tothe collection reservoir 75 of the accumulator 30 to provide the desiredmagnetic field to the collected polarized gas. As shown, the accumulator30 includes a support contact portion 211, which is configured to restagainst the support platform 210.

The Accumulator

FIGS. 3 and 4 show one embodiment of an accumulator 30 according to theinstant invention. As shown, the accumulator 30 includes a centralprimary flow path 80, a secondary flow path 95, and an exit buffer gaschannel 90. The secondary flow path or channel 95 is positionedintermediate of the primary flow path channel 80 and the buffer exitchannel 90. In a preferred embodiment, the accumulator 30 includes anozzle 110 at the lower end of the primary flow path. The nozzle 110 canhelp improve localization of the hyperpolarized gas as it impacts thecold surfaces of the reservoir 75. The nozzle 110 may also allowJoule-Thompson expansion of the cooling of the gas stream to well belowthe freezing point of the hyperpolarized gas, advantageously minimizingthe heat load on the stationary and collected hyperpolarized gas andthereby, potentially lengthening its relaxation time. In any event, theaccumulator 30 is preferably immersed in the cryogen bath 43 such thatthe reservoir 75 and about 7.62-15.24 cm (3-6 inches) of the tube isimmersed. If submerged in liquid nitrogen, the exterior wall of theouter sleeve 103 and the exterior wall or the reservoir 75 will be atabout 77° K. The freezing point of Xenon is approximately 160° K. Thus,upon exiting the primary flow path 80, the hyperpolarized gas hits thecold surface and freezes into the reservoir 75 while the buffer gasesexit the accumulator via the exit channel 90. The reservoir can includea surface coating to help prevent relaxation caused by the polarizedgas's contact with same. See U.S. Pat. No. 5,612,103, “Improved Coatingsfor the Production of Hyperpolarized Noble Gases”. Alternatively, thecontainer can be formed from or include other materials such as highpurity non-magnetic metallic films. See co-pending and co-assignedpatent application Ser. No. 09/126,448, entitled Containers forHyperpolarized Gases and Associated Methods, which is herebyincorporated by reference as if recited in full herein.

As shown in FIG. 4, the secondary flow path 95 has an inlet and outlet125, 126, respectively, positioned about 180° apart at a top portion ofthe accumulator 30. Of course, as will be appreciated by one of skill inthe art, alternative arrangements of the secondary flow path inlet andoutlet 125, 126 can also be employed. Preferably, the inlet and outlet125, 126 are configured to be above the cryogen bath 43 or otherrefrigeration means when the accumulator 30 is assembled thereto. Exceptfor its respective inlet and vent ports 125, 126, the secondary flowpath 95 is enclosed and separate from the primary flow path 80 and theexit gas path 90. As such, the secondary flow path 95 includes a sealedclosed end 96.

In operation, as shown in FIG. 6, the secondary flow path 95 providesheat to a region of the accumulator 30. Preferably, the secondary flowpath defines a heating jacket 93. The heating jacket 93 is configured toprovide a contained warm stream of a fluid, preferably a gas, around theprimary flow path 80. More preferably, the heating jacket 93 directswarm or ambient temperature nitrogen down the secondary flow path to anarea adjacent the lower portion of the primary path 80; that is, theportion of the secondary path is in close proximity to or adjacent thereservoir 75. In a preferred embodiment, the warming gas in the heatingjacket 93 is directed to the nozzle 110 area of the primary flow path 80via the secondary flow path 95. Advantageously, such a warming gas cancompensate for the undesirable tendency of this area of the primary flowpath to freeze and clog due to frozen gases trapped in the flow path 80.Further and advantageously, this configuration can also minimize anyassociated heat load which is directed into the reservoir 75 and on thecollected frozen polarized gas. The clogging problem can be particularlytroublesome in accumulators with nozzle designs, as even small amountsof build up in the reduced exit area of the nozzle 110 can block theprimary flow path 80 and decrease and even prevent further collection ofpolarized gas. “Warming” as used herein can be the application of heatat any temperature above the freezing point of selected polarized gas,i. e. above 160° K for ¹²⁹Xe.

Generally stated, the relaxation time of solid polarized gas (especially¹²⁹Xe) is strongly dependent on the temperature of the frozen gas.Stated differently, the lower the temperature of the frozen gas, thelonger the relaxation time. Thus, it is important to minimize the heatload on the accumulated frozen gas. The heat load presented by the gasstream directed down the primary flow path 80 is largely attributed tothe need to cool the buffer gas from room temperature to the cryogenictemperature (as described herein liquid nitrogen (LN₂) or 77° K. Thisheat load is estimated to be on the order of 2 W. Thus, in order tominimize the heat load on the accumulated polarized ¹²⁹Xe, it isdesirable to cool the gas steam to close to (but above) the freezingtemperature of the polarized gas prior to the exit point of the nozzle110. For ¹²⁹Xe, the buffer gas is preferably cooled to just above 160°K, below which the Xe can freeze in the nozzle potentially causing aclog or blockage. Advantageously, cooling the exit gas to 160° K can cutthe heat load on the frozen polarized gas by as much as 50%. Theconfiguration of the instant invention allows this exit channel to be socooled through the counter-flow of the buffer gas. Advantageously, thiscooling counter-flow does not overly expose the nozzle 110 to lowtemperatures because the nozzle 110 or most susceptible area of the flowpath 80 is separated from the exit channel by the heating jacket orsecondary flow channel 95.

Referring again to FIG. 4, as shown, the primary flow path 80 is definedby the shape of the inner wall 93 a of the heating jacket 93.Preferably, the inner wall 93 a circumferentially extends around anopening to define the primary flow path 80. Similarly, the outer wall 93b of the heating jacket 93 together with the outer sleeve 103 of theaccumulator 30 defines the buffer exit path 90. As shown in FIG. 6, in apreferred embodiment, the inner wall 93 a, the outer wall 93 b and theouter sleeve 103 are radially aligned. The inner wall of the heatingjacket 93 includes a stepped down portion 193 with a diameter less thanthe diameter of the preceding section of the inner wall. This steppeddown portion is configured to provide the nozzle 110 in the primary flowpath 80.

FIGS. 5 and 7 illustrate a preferred embodiment of an accumulator 30′according to the instant invention. As shown in this embodiment, theheating jacket 93 includes at least one elongated conduit 145 whichextends along a major portion of the secondary flow path 95. As theconduit 145 is exposed to cryogenic temperatures, it should be made fromsuitable substantially non-depolarizing and cryo-accepting materialssuch as PTFE and the like. Suitable materials include materials whichhave a low temperature resistance. One example of a brand of such amaterial is TEFLON™ or metallic-film coated surfaces. The conduit 145directs the warming gas down to the lower portion of the primary flowpath 80, and more preferably directs the warming gas to the nozzle area110 of the primary flow channel above the reservoir 75. As such, thelower end 145 a of the conduit is preferably positioned adjacent thenozzle 110. Once released, the warming gas travels up thecircumferentially extending secondary flow path 95 and exits at theoutlet vent 126. This warming gas can counteract the cold/cloggingeffect the counter-flow of the cold buffer gas has on the primary flowpath in the region susceptible to clogging as discussed above. Ofcourse, additional heating jacket inlets, conduits, and vents (notshown) can also be employed within the scope of the invention.

Examples of suitable diameters of the primary flow path 80, thesecondary flow path 95, and the buffer gas exit channel 90 are 6.35,12.7, and 19.05 mm (0.25, 0.50, and 0.75 inches), respectively. In oneembodiment the nozzle 110 extends along the primary flow path for about25.4 mm (1.0 inches). Preferably, the accumulator 30 is formed fromglass such as PYREX™ and is configured to withstand from about608-1013.25 kPa (6-10 atm) or more of pressure.

In operation, it is preferred that, during accumulation of frozenhyperpolarized gas, the warming gas is introduced into the secondarychannel at a rate of about 7.8658-47.2 ml/s (1-6 ft³/hour), morepreferably at the rate of about 15.732-39.329 ml/s (2-5 ft³/hr), andstill more preferably at a rate of about 23.597 ml/s (3 ft³/hr).

Preferably, during collection, the accumulator 30 operates at the samepressure as the optical pumping cell.

As discussed above, the preferred warming gas is a dry ambienttemperature N₂ (N₂ has approximately two times the heat capacity ofhelium), but the invention is not limited thereto. Exemplary preferredtemperatures of the warming gas are from about 10-26.7° C.(50°-80° F.),and m ore preferably from about 20-25.6° C. (68°-78° F.). In a preferredembodiment, a corresponding “heating gas” flow rate is set to a minimumlevel corresponding to a predetermined temperature of the warming gas;i.e., the minimum rate is set for a certain temperature below which aclog occurs, this minimum rate can be termed the “critical flow rate”.If higher temperatures are used, lower flow rates will typically berequired. Examples of other warming gases include, but are not limitedto, helium, dry air, and the like. Preferably, if higher temperature“warming” gases are used a lower corresponding flow rate is used. Incontrast, if lower temperature “warming” gases are used then a highercorresponding flow rate is used.

Advantageously, the instant invention can collect about 80-100% of thepolarized gas in the gas stream. In addition, the instant invention canyield a polarized gas product with an extended useful life. This isattributed to the improved collection and/or thawing techniques whichcan yield a polarized gas product which retains greater polarizationlevels compared to conventional techniques as will be discussed furtherbelow.

Thawing

As noted above, a preferred embodiment of the instant invention employsa compact permanent magnet a arrangement positioned around thehyperpolarized gas. Unfortunately, the magnetic field provided by suchan arrangement can be somewhat inhomogeneous. As gas is thawed, thisinhomogeneity can depolarize the hyperpolarized gas relatively quickly.Freshly thawed ¹²⁹Xe is particularly susceptible to inhomogeneityinduced decay (“loss of polarization”). For example, relaxation ofgaseous ¹²⁹Xe is particularly troublesome as it diffuses throughinhomogeneous fields. This relaxation generally scales linearly withinverse pressure of the gas. That is, at low gas pressures, which occurat the beginning of the thawing process, the inhomogeneity (fieldgradients) induced relaxation effect is the strongest. (Relaxation of¹²⁹Xe at 101.325 kPa (1 atm) of gas pressure has been measured at just22 seconds). The instant invention solves this problem by closing theisolating valves 35, 37 in the accumulator 30 during the initial thaw.As the polarized gas thaws, pressure builds up rapidly, quicklyexceeding 1 atm and building further. As the pressure rises, theremaining solid ¹²⁹Xe goes into liquid form rather than gaseous form.The liquid ¹²⁹Xe is relatively insensitive to magnetic field gradients,inhomogeneity relaxation, temperature effects, and magnetic fieldstrengths, thus making it one of the more robust forms of hyperpolarized¹²⁹Xe. Liquid ¹²⁹Xe has typical relaxation times of about 20-30 minutes.See K. L. Sauer et al., Laser Polarized LiquidXenon, Appl. Phys. Lett.(Accepted 1997). The liquid state further helps to quickly distributeheat to the remaining solid ¹²⁹Xe, thus further speeding the thaw.

In a preferred embodiment, the heating jacket 93 can also improve thethawing process of the frozen polarized gas. The instant inventionrecognizes that it is important to rapidly transform the frozenpolarized gas into a liquid state as both the solid and the gas statesof Xenon are extremely sensitive to depolarization during thetransition. For example, as solid or frozen ¹²⁹Xe is warmed to near itsmelting point, the relaxation time is dramatically reduced from 3 hoursat 77° K. to just a few seconds near the phase transition point. Inaddition, gaseous relaxation at temperatures just above the sublimationtemperature of ¹²⁹Xe is rapid, with an exponential dependence ontemperature. For example, the relaxation time of gaseous ¹²⁹Xe on agiven surface at 160° K. is only 3% as long as that at 300° K. on thesame surface. Further, during the early stages of thawing when the Xegas pressure is low, the gaseous ¹²⁹Xe is more susceptible to theinhomogeneity problems discussed above.

Conventionally, heat has been supplied to the exterior of theaccumulator during thawing. As the frozen hyperpolarized gas began tothaw it would freeze again, such as on the exit point of the primaryflow path 80. This could cause the ¹²⁹Xe to freeze and thaw more thanonce during the thawing process, as well as causing the polarized gasproduct to spend more time around the sensitive transition phase whererelaxation is more rapid.

Advantageously, the heating jacket 93 of the accumulator 30, 30′described above can additionally improve the thawing process. Turning toFIG. 8, the heating jacket or secondary flow channel 95 of theaccumulator can supply heat to the nozzle area 110 of the accumulator 30during the thawing process. Preferably the lower area of the flow pathor the nozzle area is preheated before thawing so that the nozzle 110 iswell above the freezing point of the polarized gas prior to applyingheat to the external surface of the reservoir 75. It is additionallypreferred, that during the thawing, heat is supplied to both theexterior and the interior of the cold finger. The interior heating beingpreferably applied to the lower region of the accumulator, i.e., thenozzle area. The nozzle 110 is thus warmed by the circulating fluid(preferably gas) in the heating jacket 93. Various warming gases such asthose described above can be used. Preferably, the flow rate of thewarming gas is higher than that used during the accumulation process,such as about 39.329-94.39 ml/s (5-12 ft³/hr), and more preferably atabout 78.658 ml/s (10 ft³/hr) during thaw. Similarly, the preferredtemperatures of the “warming” gas supplied during thawing are at typicalinternally controlled ambient conditions (for example room temperaturegases such as 20-25.6° C. (68-78° F.)).

For a “transported” accumulator 30, once all the ¹²⁹Xe is liquid, theisolation valve 35 is preferably opened leading to an attached evacuatedchamber or bag or other delivery means or collection vessel. Of courseeither of the valves 35, 37 can be opened depending on where thedelivery vessel or receptacle is attached (not shown). For the“on-board” accumulator, isolation valve 37 is the operative valve asdescribed above. The sudden decrease in pressure causes the liquid ¹²⁹Xeto become gaseous and exit the accumulator 30 rapidly, advantageouslythereby spending a minimum amount of time in the inhomogeneous magneticfield in the gaseous state. Similarly, if the “on-board” release isemployed, the isolation valve 37 is opened and the gas flows throughvalve 47 and exits outlet 50 into a delivery vessel. Conventionalmethods of thawing included opening the cold finger (accumulator) to thevessel to be filled and then starting the thaw. This thaw couldtypically take 30 seconds or more to complete for single patient doseamounts. In comparison and advantageously, the instant thaw method canbe completed in less than about 10 seconds, and preferably in less thanabout 5-6 seconds for single dose amounts of frozen hyperpolarized gas.A typical patient dose is from about 0.20-1.25 liters (“L”) andpreferably about 0.5-1.0 L. The conversion weight is about 5.4 grams/Lof Xe. Similarly, the density of solid Xe is about 3.1 g/cm³, and acorresponding patient volume of polarized frozen Xe can be calculated atabout 1.8 cm³/L.

Advantageously, observations of the instant thawing method indicate areliable factor of about 2 or more improvement in the final polarizationlevel of thawed ¹²⁹Xe as compared to that thawed by conventionalmethods.

Referring now to FIGS. 12A and 12B, FIG. 12A illustrates thepolarization results obtained by a conventional thaw technique whileFIG. 12B graphically illustrates results obtained by the improved thawmethod of the instant invention as described above. Each of the graphsplot % polarization of ¹²⁹Xe after thaw in relationship to the total gasflow rate through the polarization cell 22 (and therefore the entireunit). The corresponding ¹²⁹Xe flow rate is the % of the total gas mix.In the example shown, ¹²⁹Xe makes up about 1% of the total gas mix, thusthe ¹²⁹Xe-flow rate is the total flow rate divided by 100. For exampleat a flow rate of 1000 standard cm³ (standard cubic centimeters perminute (“sccm”)), ¹²⁹Xe is typically accumulated at the rate of 10 cm³per min or 600 cm³ per hour. Higher flow rates are desired to increasethe through-put of ¹²⁹Xe. However, polarization is reduced at higherflow rates. This is attributed to the reduced time that the ¹²⁹Xe spendsin residence time in spin exchange contact with the optically pumped Rbat higher flow rates. That is, the Xe residence time in the cell 22 cangenerally be described mathematically as equal to the gas pressuremultiplied by the cell volume divided by the flow rate (PV/{dot over(m)}).

FIG. 12A shows the conventional thaw technique yields scatteredpolarization results which are attributed to random polarization lossesmainly occurring during thawing. FIG. 12B tracks with the opticalpumping characteristics described above and now produces predictablepost-thaw polarization levels corresponding to the accumulation flowrate.

As shown in FIG. 12B, when thawing according to the improved methoddescribed above (under pressurization and with internal and externalheating), for flow rates below 1000 sccm (or standard cm³/min),polarization levels after thaw of above 10% are reliably achieved. Theresults shown in this figure represent a 190 cm³ volume of ¹²⁹Xe (and Rbpolarization levels of about 0.25-0.49). Of course, as will beappreciated by one of skill in the art, different volumes (i.e., largeror smaller) of the polarized gas will have different relative valuesassociated therewith. For example, larger volumes of ¹²⁹Xe takes longertimes to polarize, therefore at the same flow rates, the polarization ofthe larger volume will be less than that shown in FIG. 12B. Stateddifferently, for larger amounts of polarized gas, the associatedpolarization curve will drop below the values shown relative to that foran exemplary 190 cm³ volume of polarized gas as shown in FIG. 12B. Also,typically, larger amounts of polarized gas can result in a larger lossattributed to solid-phase relaxation. However, as shown by the graph,the instant invention now provides a frozen gas thaw method whichresults in a post-thaw polarization curve which predictably follows theinitial polarization curve. In contrast, as shown by FIG. 12A, theconventional polarization level after thaw is highly unpredictable, withan average of about 4.4%. Indeed, at about 900 sccm (standard cm³/min),the polarization point is about 2.16% while prediction is 18.7%, thusmaking the retention fraction a low 12.2% (losing about 87.8% of thestarting polarization). Unlike the conventional method, the instantinvention produces polarization levels after thaw that predictablycorresponds to the flow rate used during accumulation.

FIG. 13 illustrates experimental and theoretical polarization levelsbefore and after thawing. The experimental flowing curve shows thepolarization levels achieved before freezing (the level measured as the¹²⁹Xe exits the pumping cell 22). The experimental data points on thegraph represent thawed data points achieved by thawing the collected,frozen polarized gas according to the present invention. Theexperimental data confirms that the methods of the instant inventionimprove the predictability of the polarization retention fraction nowachievable as well as increases the value of the polarization retentionfraction (amount of polarization retained post-thaw relative to thatattained prior to freeze).

FIG. 13A illustrates a flow curve used to predict polarization levels asexpected from a thawed polarized xenon product, this curve representingpost-thaw polarization levels achievable absent polarization lossesduring freezing and thawing. This curve includes losses from normalrelaxation of solid Xe (which can be generally estimated to beapproximately 2 hours at 77° K). As shown, low flow rates typically havean associated relatively large polarization loss. This is because, atlow flow rates, the accumulation time can be extensive and the ice “T1”then plays a larger or more dominant role. As shown, the polarizationretention fraction achieved using the freezing and thawing methods ofthe instant invention is above 40% for all flow rates, and the averageis about 49.9%. Therefore, as shown in FIG. 13A, this polarizationretention fraction is substantially insensitive to flow rate. The belowlisted data shows exemplary polarization retention fractions nowachievable.

Flow Rate Polarization (P)_(theory) P_(exper.) Retention Fraction 300 2412.66 52.8% 600 22.1 11.18 50.6% 900 18.7 9.30 49.7% 1200 15.9 7.8349.2% 1500 13.75 6.73 48.9% 1800 12.08 5.90 48.8% 2000 11.1 5.43 48.9%

For example, a data point at a flow rate of 600 sccm has a theoreticalpolarization level of 22.1 and a corresponding experimental data pointof 11.18 polarization after thaw. The initial polarization level(before- accumulation/freezing) for this flow rate is 22.1%. Therefore,the polarization retention fraction after the freeze/thaw process is11.18/22.1 or 50.6%. Thus, advantageously, the instant thawing techniqueretains at least 30% of the initial polarization level and based on thisdata preferably above 40% of the initial polarization level, and mostpreferably above 45%. Further the improved retention rate increases thethawed polarization level by an order of magnitude (now reliably andpredictably above about 10% in contrast to conventional thawedpolarization levels of about 2%).

Although particularly suited for ¹²⁹Xe, the instant thawing method canalso successfully be employed with other hyperpolarized noble gases.Further, it will be appreciated by those of skill in the art, that thecryogen used to freeze the polarized gas is not limited to liquid N₂.However, if alternate refrigeration sources or cryogens are used thenflow rates, accumulation rates, “warming” gas temperatures and the likeshould be adjusted accordingly. Further, it is desired to userefrigeration sources with temperatures at least as low as liquidnitrogen (77 K) for collection of the polarized gas. Lower temperaturesincrease the T1 time of the solid polarized gas which results inincreased relaxation times. For example, polarized gases frozen atliquid nitrogen temperatures have an ice relaxation time (T1) ofapproximately 2.8 hours while polarized gases frozen at liquid heliumtemperatures have an ice relaxation time (T1) of approximately 12 days.Therefore, in order to achieve higher polarization levels after thawing,the thawing is preferably performed within the corresponding T1 timeperiod.

FIGS. 9, 10, and 11 are block diagrams of methods associated with theinstant invention. The order of the methods is not meant to be limitedby the block numbers and order shown. Additional steps can also beincluded as operationally described hereinabove.

FIG. 9 shows steps for accumulating or collecting frozen polarized gasaccording to one embodiment of the instant invention A gas mixturecomprising a polarized gas is directed into collection path (Block 900).The polarized gas is received into the accumulator in the collectionpath. The accumulator has an inlet channel, a collection reservoir, andan exit channel (Block 910). The collection reservoir is exposed totemperatures below the freezing point of the polarized noble gas (Block920). The polarized gas is trapped in a substantially frozen state inthe collection reservoir (preferably a total solid frozen state)(Block930). The remainder of the gas mixture is routed into the exit channel(Block 940). A portion of the inlet channel in the accumulator is heatedto facilitate the flow of the gas mixture therethrough (Block 950). Theheating step (Block 950) is preferably carried out by introducing a gasseparate from the gas mixture to conductively heat a predetermined areaof the inlet channel, the separate gas being contained apart from theinlet and exit paths. The contained separate gas is then circulatedabout a portion of the inlet path to reduce the likelihood of blockagealong the inlet path attributed to the exposing step.

FIG. 10 illustrates a method for thawing frozen polarized gas accordingto a preferred embodiment of the present invention. A sealed containeris provided which includes an interior flow path and a collectionchamber for holding frozen polarized gas (Block 1000). The frozen gas isexposed to a magnetic field (Block 1005). A portion of the interior flowpath adjacent the collection chamber is heated (Block 1010). Theexterior of the sealed container is also heated (Block 1020). The frozengas is liquefied during the heating steps such that a minimum amount ofthe polarized gas transitions to the gaseous phase (and conversely, asubstantial amount of the polarized gas transitions directly to theliquid phase) (Block 1030). Preferably, the liquefying step is carriedout by closing the isolation valves and sealing the container allowingthe pressure to build to a predetermined level, the level correspondingto the time it takes to provide an “instantaneous” thaw. Stateddifferently, the valves remain closed for as short a period as possible(as described above, less than about 10 seconds for a single patientdose), the period corresponding to the time it takes to achievesubstantially full gas pressure upon opening the accumulator isolationvalve. The release pressure can be calculated according to a liquid Xevapor pressure curve. See V. A. Rabinovich et al., ThermophysicalProperties of Neon, Argon, Krypton, and Xenon (Hemisphere PublishingCorp., Wash, 1988). An exemplary pressure release is thought to be lessthan approximately 506.625-1013.25 kPa (5-10 atm) (and at least lessthan about 1722.525 kPa (17 atm)) for a 0.5 L accumulation in a 30 cm³accumulator at a temperature below 200 K. This value will be differentfor different cold finger volumes, different accumulation volumes, andthe temperature of the gas in liquid Xe. The Sauer et al. reference,supra, indicates that for Xe at 161.4 K, P=81.06 kPa (0.81atm), and thetriple point 289.7 K, P=5775.525 kPa (57 atm), at 240 K, P=4053 kPa(40atm). Thus, as indicated by Block 1040, the gas pressure is releasedfrom the sealed container as soon as the liquid state is achieved. It isalso preferred that the interior be heated as described above.

FIG. 11 illustrates a method for extending the useful polarization lifeof a polarized gas product according to one embodiment of the presentinvention. A magnetic field is provided (Block 1100). The polarized gasproduct is frozen in the presence of the magnetic field (Block 1110). Aquantity of the frozen polarized gas is sealed in a containment device(Block 1115). The polarized gas is thawed in the presence of a magneticfield (Block 1120). A substantial quantity of the frozen gas isconverted directly into the liquid phase in the sealed container duringthe thawing step (Block 1130). Although not shown in this figure,various other steps can be employed along the lines describedhereinabove. (For example, other steps can include, but are not limitedto, decreasing the amount of ¹³¹Xe in the enriched gas mixture, heatingthe interior of the flow path, using a nozzle to direct the flow of gas,depressurizing the containment device by opening the valves causing theliquid to become gas and releasing the polarized gas to a interface suchas a bag or other delivery device).

The foregoing is illustrative of the present invention and is not to beconstrued as limiting thereof. Although a few exemplary embodiments ofthis invention have been described, those skilled in the art willreadily appreciate that many modifications are possible in the exemplaryembodiments without materially departing from the novel teachings andadvantages of this invention. Accordingly, all such modifications areintended to be included within the scope of this invention as defined inthe claims. In the claims, means-plus-function clause are intended tocover the structures described herein as performing the recited functionand not only structural equivalents but also equivalent structures.Therefore, it is to be understood that the foregoing is illustrative ofthe present invention and is not to be construed as limited to thespecific embodiments disclosed, and that modifications to the disclosedembodiments, as well as other embodiments, are intended to be includedwithin the scope of the appended claims. The invention is defined by thefollowing claims, with equivalents of the claims to be included therein.

That which is claimed is:
 1. A method for collecting polarized noblegases, comprising the steps of: directing a gas mixture comprising apolarized noble gas and a second gas along a collection path and into anaccumulator; receiving the gas mixture into the accumulator positionedin the collection path, the accumulator having an inlet channel, acollection reservoir, and an exit channel; cooling the collectionreservoir to temperatures below the freezing point of the polarizednoble gas; trapping polarized noble gas in a substantially frozen statein the collection reservoir; passing the remainder of the gas mixtureincluding the second gas into the exit channel; and heating a portion ofthe inlet channel in the accumulator to facilitate the flow of the gasmixture therethrough.
 2. A method according to claim 1, wherein saidheating step comprises the steps of: introducing a gas separate from thegas mixture to heat a predetermined area of the inlet channel, theseparate gas being contained apart from the inlet and exit channels, andthe collection reservoir; and circulating the gas separate from the gasmixture about a portion of the inlet channel to provide conductive heatto selected portions of the inlet channel and reduce the likelihood ofblockage along the inlet channel attributed to said exposing step.
 3. Amethod according to claim 2, wherein said heating step is an adjustableheating step whereby the heat supplied is increased or decreased byadjusting at least one of the temperature or the rate of flow of thecirculating gas.
 4. A method according to claim 2, wherein saidpolarized gas is ¹²⁹Xe.
 5. A method according to claim 1, wherein saiddirecting step includes flowing the gas mixture through a directionalnozzle into the collection reservoir.
 6. A method according to claim 1,wherein said cooling step includes immersing a lower portion of thereservoir into a liquid cryogen bath.
 7. A method according to claim 1,wherein said heating step is provided by the steps of: circulating roomtemperature nitrogen gas around the outside perimeter of at least aportion of the inlet channel; and capturing the nitrogen gas and ventingto atmosphere away from the frozen accumulated noble gas.
 8. A methodaccording to claim 1, further comprising the steps of: accumulatingpolarized noble gas in the collection reservoir; and exposing the gas toa magnetic field during accumulation.
 9. A method according to claim 8,further comprising the steps of: detaching the accumulator from aportion of the collection path; and transporting the accumulator withfrozen polarized gas in the presence of a magnetic field to a remotesite.
 10. A method according to claim 1, wherein said gas mixturecomprises Xenon and an enriched amount of ¹²⁹Xe, and wherein less thanabout 3.5% of the isotope ¹³¹Xe is in said gas mixture.
 11. A method ofthawing frozen polarized gas, comprising the steps of: providing asealed container having an interior flow path and a collection chamber,the collection chamber holding frozen polarized gas therein; exposingthe frozen polarized gas to a magnetic field; heating a portion of theinterior flow path adjacent the collection chamber by circulating afluid or fluid mixture in a chamber positioned adjacent to at least aportion of the interior flow path of the sealed container such that thecirculating fluid is in fluid isolation from the frozen polarized gas;and heating the exterior of the sealed container.
 12. A method accordingto claim 11, further comprising the step of liquefying a substantialportion of the frozen polarized noble gas during thawing.
 13. A methodaccording to claim 12, wherein the polarized gas retains about 30% ormore of its initial polarization upon thawing.
 14. A method according toclaim 12, wherein the sealed container is operatively associated with apair of isolation valves, and the step of liquefying is carried out byclosing the valves and allowing the pressure in the container to rise toa predetermined level during said heating steps.
 15. A method accordingto claim 14, further comprising the steps of: opening at least one ofthe valves to decrease the pressure in the container causing theliquified gas to become gaseous; and directing the flow of the gas to areceptacle.
 16. A method according to claim 11, wherein said interiorheating step is initiated before said exterior heating step.
 17. Amethod according to claim 11, wherein said polarized gas comprises¹²⁹Xe.
 18. A method according to claim 11, wherein said interior heatingstep comprises conductively heating at least a portion of the interiorflow path by circulating a gas in a chamber configured to encase atleast a portion of the interior flow path.
 19. A method according toclaim 18, wherein said gas is directed towards a bottom of the interiorflow path above the collection chamber through a conduit.
 20. A methodaccording to claim 11, wherein a single patient dose amount of thepolarized gas is thawed in less than 10 seconds.